AZ's cediranib falls short again in ovarian cancer combination

AstraZeneca and Merck & Co’s latest attempt to revive an old pipeline drug cediranib has failed as it did not improve survival compared with chemotherapy in advanced ovarian cancer, in combination with the PARP drug Lynparza.

As competitors from the likes of GlaxoSmithKline, Clovis, and Pfizer come to market, AZ and Merck are looking to combine Lynparza with other drugs to make it more effective.

However things have not gone to plan with a potential combination with cediranib, a vascular endothelial growth factor receptor (VEGFR) drug that has been in AZ’s pipeline for years.

In the past AZ has tried to combine cediranib, which works by blocking blood vessels supporting tumour growth, with several other cancer drugs.

But efforts to combine cediranib with other drugs such as Roche’s Avastin (bevacizumab) in colorectal cancer have drawn blanks in clinical trials.

And cediranib and Lynparza last year fell short in the BAROCCO study in patients with platinum-resistant ovarian cancer, which included patients with and without BRCA mutations.

Unfortunately for AZ the story was the same in the phase 3 GY004 trial testing efficacy and safety of cediranib added to Lynparza versus platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer.

The trial missed its primary goal in the trial’s intent-to-treat population of a statistically significant improvement in progression-free survival with cediranib and Lynparza versus platinum-based chemotherapy.

Cediranib is also being tested in combination with Lynparza in advanced ovarian cancer in the phase 2 CONCERTO trial, and the phase 3 ICON9 trial sponsored by University College, London.

GY004 was led by NRG Oncology and sponsored by the US National Cancer Institute (NCI).

José Baselga, AZ’s executive vice president for oncology R&D, said: “Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer. We will work closely with NRG Oncology and the NCI to review the full results to inform our ongoing research.”